Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholesterol balance studies were carried out twice in a young male patient with homozygous familial hypercholesterolemia. At 13 mo, cholesterol balance in this patient averaged 31.3 mg/kg per d, and bile acid excretion was 12.0 mg/kg per d; at 3 yr, results were similar, 27.3 and 15.5 mg/kg per d for cholesterol balance and bile acids, respectively. A normal boy of 3 yr was also studied for comparison with the second study in our patient. Cholesterol balance and bile acid outputs in the normal child were 11.5 and 3.3 mg/kg per d, respectively. Thus, in comparison with the normal child, the patient with homozygous familial hypercholesterolemia had a marked increase in synthesis of cholesterol and bile acids. Although synthesis of bile acids was high in this patient, the fraction of newly synthesized cholesterol converted into bile acids (40-56%) was in the normal range; this suggests that the enhanced output of bile acids was secondary to an increased synthesis of cholesterol and not to malabsorption of bile acids, which likely would have produced a higher fractional conversion. Although our patient has been studied at a younger age than any reported in the literature, two similar children 5 and 6 yr of age were also observed to have elevated cholesterol synthesis. This finding contrasts with those in older children with the homozygous as well as heterozygous forms of this disease who appear to have normal synthesis of cholesterol and bile acids. Therefore, increased synthesis of cholesterol seems to be characteristic of early homozygous familial hypercholesterolemia, and may be a manifestation of a loss of feedback inhibition of cholesterol synthesis secondary to an absence of specific cell-surface receptors for low density lipoproteins. However, as children with this disease grow older, other mechanisms may come into play to restore cholesterol synthesis to normal levels.
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PMID:Elevated cholesterol and bile acid synthesis in a young patient with homozygous familial hypercholesterolemia. 46 90

Results related to long term treatment with Colestipol (a new resin sequestering bile acids) in 23 subjects with familial hypercholesterolaemia, 12 with Type IIA, 8 with Type IIB and 3 homozygotes are reported. Patients were given 15 g/day active drug for a period of 12 months and a double dose (30 g/day) for a successive period of 4 months along with a low cholesterol, low saturated fat, polyunsaturated fat-rich diet. Mean cholesterol decrease was --42 +/- 18 mg/dl (P less than 0.05) after 12 months of 15 g/day Colestipol and --69 +/- 17 mg/dl (P less than 0.01) after the following 4 months of 30 g/day Colestipol. The difference between the two periods of treatment (15 g and 30 g/day was not statistically significant. A slight but not significant increase in triglyceride levels was observed. Serum uric acid showed a significant increase throughout the entire period of treatment. No malabsorption syndrome or signs of toxicity were seen. Most frequent side effects were constipation, nausea, and metheorism which, with the exception of 4 cases which were withdrawn from the study, were reported as being transitory and mild.
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PMID:Long-term effects of colestipol (U-26,597 A) on plasma lipids in familial type II hyperbetalipoproteinaemia. 120 Nov 45

In the past 5 years, many different mutations in the apolipoprotein (apo) B gene have been described that affect plasma cholesterol levels. More than 20 different mutations in the apoB gene have been shown to cause familial hypobetalipoproteinaemia, a condition characterized by abnormally low plasma concentrations of apoB and LDL cholesterol. Almost all of the mutations are nonsense or frameshift mutations that interfere with the translation of a full-length apoB100 molecule. Many, but not all, of these apoB gene mutations result in the synthesis of a truncated species of apoB that can be detected within the plasma lipoproteins. Familial hypobetalipoproteinaemia heterozygotes are almost always asymptomatic and have LDL cholesterol levels about one-quarter to one-third of those of unaffected family members. Several homozygotes and compound heterozygotes for familial hypobetalipoproteinaemia have been described. In these individuals, the LDL cholesterol levels are extremely low, usually less than 5 or 10 mg dl-1, and the clinical phenotype is variable, ranging from completely asymptomatic to severe problems related to intestinal fat malabsorption. One missense mutation in the apoB gene (an Arg----Gln substitution at apoB amino acid 3500) is associated with very poor binding of apoB100 to the cellular LDL receptor. This syndrome has been designated familial defective apolipoprotein B (FDB). The amino-acid substitution at residue 3500 delays the clearance of LDL from the plasma and results in hypercholesterolaemia. In some Western populations, the frequency of FDB heterozygotes appears to be as high as 1 in 500 individuals.
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PMID:Apolipoprotein B gene mutations affecting cholesterol levels. 161 87

To evaluate the value of plasma cholesterol precursor sterols in the detection of bile acid malabsorption we measured these sterols in 14 familial hypercholesterolaemia patients, seven with and seven without an ileal exclusion. In the operated subjects bile acid malabsorption had induced a 4.8-fold increase in cholesterol synthesis, accompanied by a 1.9-5.1-fold increase in the plasma content of the eight cholesterol precursor sterols studied. There was no overlap between the two groups in any of these sterols, when total and free sterols were considered, and only three of the esterified sterols overlapped. The tri- and dimethyl sterols were mostly unesterified, monomethyl sterols modestly esterified and the demethylated sterols, especially desmosterol, were mainly esterified. The plasma lathosterol content segregated most clearly the patients with bile acid malabsorption from the controls. The lowest lathosterol value of the operated patients was 2.5-fold higher than the highest value of the control patients. Because lathosterol is the most abundant of the plasma cholesterol precursor sterols and is relatively easy to quantitate, it is suggested that plasma lathosterol measurement can be used in the detection of bile acid malabsorption.
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PMID:Evaluation of bile acid malabsorption by plasma cholesterol precursor sterols in familial hypercholesterolaemia patients with and without ileal exclusion. 321 53

A plant sterol, sitosterol, was quantitated in very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) and related to faecal steroids and cholesterol absorption in heterozygous familial hypercholesterolaemia patients with (n = 7) and without ileal bypass (n = 6). The latter had resulted in severe bile acid malabsorption but fractional cholesterol absorption was within low control limits. Serum total and LDL cholesterol and apoprotein B levels were reduced, whereas HDL cholesterol, apoprotein A-I, VLDL and HDL sitosterol concentrations were increased by the ileal exclusion, and the increase in LDL and serum total sitosterol levels was insignificant. In terms of mmol/mol of cholesterol or apoprotein B, however, the LDL and total sitosterol contents were higher in the subjects who had undergone operation. For an unknown reason the sitosterol content increased gradually within the lipoprotein particles from the lighter to the heavier lipoproteins, and the enrichment was similar in the two groups. Dietary sitosterol intake, indicated by faecal sitosterol excretion, was similar in the two groups. The contents of serum total and LDL sitosterol were positively correlated with the dietary sitosterol intake in both groups, and with the fractional cholesterol absorption only in the group not subject to operation. These associations were less consistent for sitosterol contents in other lipoproteins. We conclude that normally the serum sitosterol content reflects cholesterol absorption efficiency even in patients with familial hypercholesterolaemia, provided the dietary sitosterol intake is quite constant. In addition, for unknown reasons ileal exclusion leads to an increased lipoprotein sitosterol content.
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PMID:Effect of ileal exclusion on lipoprotein sitosterol in familial hypercholesterolaemia. 335 98

The National Heart, Lung, and Blood Institute is currently sponsoring a multicenter clinical trial to evaluate the long-term efficacy of partial ileal bypass in the prevention of recurrent myocardial infarction in hypercholesterolemia patients. Thus we felt that a report of our clinical results with this intervention at the Montreal Heart Institute during the last 11 years would be of interest. Twenty patients with type II hyperlipoproteinemia and a mean age of 38 (range 25-54) years underwent partial ileal bypass between March 1971 and April 1978. This intervention was associated with aortocoronary bypass surgery in 11 patients. All patients were followed at regular intervals. The mean survival time was 70.7 (range 1-123) months. Two deaths were observed during follow-up, one from an acute myocardial infarction and the other from ventricular fibrillation, respectively, 1 month and 1 and one-half years after partial ileal bypass. The ileal bypass was undone twice because of gastrointestinal problems including a malabsorption syndrome and repeated episodes of subocclusion. A progressive decrease of the effects of the operation on serum cholesterol was noted, from a 33 per cent reduction at 3 months to 43 per cent at 2 years and 16 per cent at 6 years. Two patients presented an acute myocardial infarction respectively 3 and 4 years after the operation, respectively, and one patient suffered a right-sided hemiplegia at age 30, 12 months after the operation. Of 14 patients with angina pectoris preoperatively (class III in 10), eight remained symptomatic postoperatively (class I and II angina in five).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Partial ileal bypass in type II familial hypercholesterolemia. Eleven-year experience at the Montreal Heart institute. 636 76

The radiographic features of five patients with arteriohepatic dysplasia are presented. These patients had congenital intrahepatic cholestasis with elevated serum bile acids, vertebral body abnormalities of shape and/or segmentation, shortened digits, and congenital heart disease, particularly peripheral pulmonic stenosis. They also had dysmorphic facies, eye abnormalities, hypercholesterolemia, and mild fat malabsorption. Some of the patients had neurologic, endocrine, and/or renal abnormalities as well, and they may have had hoarse voices due to vocal cord nodules. Variability in expression of the syndrome and vertical transmission suggest an autosomal dominant pattern of inheritance.
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PMID:Arteriohepatic dysplasia: radiologic features of a new syndrome. 677 28

For decades, research interest has focused on hypertriglyceridemia and hypercholesterolemia, because of their association with atherosclerosis. Recently, however, increasing attention has been paid to rare hypolipidemic states that can cause adverse consequences in young patients. Studies of genetic disorders of fat transport have afforded new insights into the mechanisms involved in intestinal lipid handling and lipoprotein metabolism. This article reviews briefly the current state of knowledge about inherited lipoprotein deficiencies, including abetalipoproteinemia, hypobetalipoproteinemia and chylomicron retention disease. These disorders share many common characteristics: they all cause fat malabsorption, low levels of circulating lipids and fat-soluble vitamins, failure to thrive in early childhood, ataxic neuropathy and visual impairment. However, their etiology is genetically different. Abetalipoproteinemia is caused by the absence of microsomal transfer protein, whereas hypobetalipoproteinemia is due to defects in the apolipoprotein B gene. The etiopathogenesis of chylomicron retention disease is as yet unexplained. Research on these rare, inherited fat disorders of absorption will continue to provide significant advances in our understanding of human physiology and may yield novel therapeutic approaches to atherosclerosis.
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PMID:The genetic basis of primary disorders of intestinal fat transport. 888 69

Hypercholesterolemia is an important atherogenic risk factor in type II diabetes, and although coronary artery disease (CAD) is frequent in these patients, it is not known whether cholesterol and lipoprotein metabolism differ in patients with (CAD+) and without CAD (CAD-). Our aim was to study cholesterol metabolism and lipoprotein kinetics in mildly hypercholesterolemic type II diabetic men with and without CAD under similar dietary conditions. Despite similar serum and lipoprotein cholesterol levels, and kinetics of total and dense LDL apo B, light and dense LDL particles were cholesterol-enriched only in CAD+ subjects. Apolipoprotein A-II level was lower in CAD+ than in CAD- subjects (27.1 +/- 0.7 versus 30.9 +/- 0.7 mg/dl, P < 0.05), HDL cholesterol and apolipoprotein A-I kinetics were similar in the two groups. Cholesterol absorption was significantly higher in the CAD+ versus CAD- subjects (27 +/- 2 versus 20 +/- 3%, P < 0.05). In multiple logistic stepwise regression analysis with CAD as the dependent variable, cholesterol absorption efficiency and serum plant sterol/cholesterol proportions were the only variables significantly associated with CAD. In conclusion, in mildly hypercholesterolemic type II diabetic patients, the only metabolic parameter differentiating CAD patients from non-CAD ones was significantly higher cholesterol absorption efficiency in the coronary patients, which could contribute to the finding of the atherogenic cholesterol-rich dense LDL subfraction in these patients. Thus, a treatment causing cholesterol malabsorption by sitostanol alone or in combination with statin could be beneficial in these patients.
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PMID:Cholesterol absorption and lipoprotein metabolism in type II diabetes mellitus with and without coronary artery disease. 890 58

In 1990 Scopinaro's technique of biliopancreatic diversion with distal gastrectomy (DG) and gastroileostomy was modified. A sleeve gastrectomy with duodenal switch (DS) was used instead of the distal gastrectomy; and the length of the common channel was made 100 cm instead of 50 cm. A questionnaire and a prescription for blood work were sent to 252 patients who underwent DG a mean 8.3 years ago (range 6-13 years) and 465 patients who underwent DS 4.1 years ago (range 1.7-6.0 years). The questionnaire response rate was 93%, and laboratory work was completed for 65% of both groups. The mean weight loss after DG was 37 +/- 21 kg and after DS 46 +/- 20 kg. There were fewer side effects after DS: The number of daily stools was lower (p < 0.0002), as was the prevalence of diarrhea (p < 0.01), vomiting (p < 0.001), and bone pain (p < 0.001). Greater benefits related to several aspects of life were reported after DS than DG (p < 0.0001). The mean serum levels of ferritin, calcium, and vitamin A were higher (p < 0.001), and parathyroid hormone was lower. The yearly revision rate for excessive malabsorption was 1.7% per year after DG and 0.1% per year after DS. The two procedures were equally efficient for treating co-morbid conditions such as diabetes, hypertension, and hypercholesterolemia. Biliopancreatic diversion with sleeve gastrectomy/duodenal switch and a 100-cm common limb was shown to produce greater weight loss with fewer side effects.
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PMID:Biliopancreatic diversion with duodenal switch. 971 20


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